Yu Zhiqi, Xu Jun, Liu Jinbao, Wu Jing, Lee Chan Mi, Yu Li, Hu Jim
State Key Lab of Respiratory Disease and Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510120, China.
Protein Modification and Degradation Laboratory, Department of Pathophysiology, Guangzhou Medical University, Guangdong, China.
Mediators Inflamm. 2015;2015:547928. doi: 10.1155/2015/547928. Epub 2015 Jun 21.
Cystic fibrosis (CF) patients suffer from chronic airway inflammation with excessive neutrophil infiltration. Migration of neutrophils to the lung requires chemokine and cytokine signaling as well as cell adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1), which plays an important role in mediating adhesive interactions between effector and target cells in the immune system. In this study, we investigated the relationship between ICAM-1 and epithelium-specific ETS-like transcription factor 1 (ESE-1) and found that ICAM-1 expression is upregulated in cell lines of CF (IB3-1) as well as non-CF (BEAS-2B and A549) epithelial origin in response to inflammatory cytokine stimulation. Since ESE-1 is highly expressed in A549 cells without stimulation, we examined the effect of ESE-1 knockdown on ICAM-1 expression in these cells. We found that ICAM-1 expression was downregulated when ESE-1 was knocked down in A549 cells. We also tested the effect of ESE-1 knockdown on cell-cell interactions and demonstrate that the knocking down ESE-1 in A549 cells reduce their interactions with HL-60 cells (human promyelocytic leukemia cell line). These results suggest that ESE-1 may play a role in regulating airway inflammation by regulating ICAM-1 expression.
囊性纤维化(CF)患者患有慢性气道炎症,伴有大量中性粒细胞浸润。中性粒细胞向肺部的迁移需要趋化因子和细胞因子信号传导以及细胞粘附分子,如细胞间粘附分子-1(ICAM-1),它在介导免疫系统中效应细胞与靶细胞之间的粘附相互作用中起重要作用。在本研究中,我们研究了ICAM-1与上皮特异性ETS样转录因子1(ESE-1)之间的关系,发现CF(IB3-1)以及非CF(BEAS-2B和A549)上皮来源的细胞系在炎症细胞因子刺激下ICAM-1表达上调。由于ESE-1在未受刺激的A549细胞中高表达,我们检测了敲低ESE-1对这些细胞中ICAM-1表达的影响。我们发现,在A549细胞中敲低ESE-1时,ICAM-1表达下调。我们还测试了敲低ESE-1对细胞间相互作用的影响,并证明在A549细胞中敲低ESE-1会减少它们与HL-60细胞(人早幼粒细胞白血病细胞系)的相互作用。这些结果表明,ESE-1可能通过调节ICAM-1表达在调节气道炎症中发挥作用。